Defining the role of NMDA receptors in anesthesia: are we there yet?

Andrey B Petrenko; Tomohiro Yamakura; Kenji Sakimura; Hiroshi Baba

doi:10.1016/j.ejphar.2013.11.039

Defining the role of NMDA receptors in anesthesia: are we there yet?

Eur J Pharmacol. 2014 Jan 15:723:29-37. doi: 10.1016/j.ejphar.2013.11.039. Epub 2013 Dec 11.

Authors

Andrey B Petrenko¹, Tomohiro Yamakura², Kenji Sakimura³, Hiroshi Baba²

Affiliations

¹ Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahi-machi, Chuo-ku, Niigata 951-8510, Japan. Electronic address: abpetr@med.niigata-u.ac.jp.
² Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahi-machi, Chuo-ku, Niigata 951-8510, Japan.
³ Department of Cellular Neurobiology, Brain Research Institute, Niigata University, 1-757 Asahi-machi, Chuo-ku, Niigata 951-8585, Japan.

PMID: 24333550
DOI: 10.1016/j.ejphar.2013.11.039

Abstract

N-methyl-d-aspartate (NMDA) receptors are important in mediating excitatory neurotransmission in the nervous system. They are preferentially inhibited by some general anesthetics and have, therefore, been implied in the mediation of their effects. This review summarizes the main research findings available related to NMDA receptors and their role in anesthesia. The contribution of NMDA receptors to the anesthetized state is discussed separately for each of its components: amnesia, analgesia, unconsciousness and immobility. Anesthetic-induced unconsciousness and immobility have received the most attention in the research community and are the main focus of this review. In the overall perspective, however, studies using pharmacological or electrophysiological approaches have failed to reach definitive conclusions regarding the contribution of NMDA receptors to these anesthetic endpoints. None of the studies have specifically addressed the role of NMDA receptors in the amnestic effect of general anesthetics, and the few available data are (at best) only indirect. NMDA receptor antagonism by general anesthetics may have a preventive anti-hyperalgesic effect. The only and most extensively used genetic tool to examine the role of NMDA receptors in anesthesia is global knockout of the GluN2A subunit of the NMDA receptor. These animals are resistant to many intravenous and inhalational anesthetics, but the interpretation of their phenotype is hindered by the secondary changes occurring in these animals after GluN2A knockout, which are themselves capable of altering anesthetic sensitivity. Generation of more sophisticated conditional knockout models targeting NMDA receptors is required to finally define their role in the mechanisms of anesthesia.

Keywords: Amnesia; Anesthesia; Cyclopropane (PubChem CID: 6351); Desflurane (PubChem CID 42113); GluN2A subunit knockout mice; Halothane (PubChem CID: 3562); Hypnosis; Immobility; Isoflurane (PubChem CID: 3763); Ketamine hydrochloride (PubChem CID: 15851); N-methyl-d-aspartate receptor; Nitrous oxide (PubChem CID: 948); Pentobarbital sodium (PubChem CID: 23676152); Phencyclidine (PubChem CID: 6468); Sevoflurane (PubChem CID: 5206); Xenon (PubChem CID: 23991).

Publication types

Review

MeSH terms

Anesthesia*
Anesthetics / pharmacology*
Anesthetics / therapeutic use
Animals
Humans
Protein Subunits
Receptors, N-Methyl-D-Aspartate / chemistry
Receptors, N-Methyl-D-Aspartate / metabolism*

Substances

Anesthetics
Protein Subunits
Receptors, N-Methyl-D-Aspartate